Continuation is planned for a long-term study of the contribution of plus 21 mosaicism to the occurrence of plus 21 offspring. a) Determine quantitative dermal indices of father, mother and plus 21 index case. Establish if either parent has dermal microsymptoms. b) Perform chromosome analyses on peripheral blood (and skin) to look for 46/47, plus 21 mosaicism in father or mother (count 50 cells), and to confirm 47/plus 21 in index case. c) Perform Q- and C-banding, and chromosome measurements to identify polymorphisms for chromosome 21 in index case, father, and mother. If possible, establish which parent contributed the extra chromosome and relate to dermal microsymptoms. d) Determine the occurrence of plus 21 in subsequent pregnancies monitored prenatally. e) Determine the occurrence of 46/47, plus 21 in monitored pregnancies of women age 40 and over (count 50 cells). In a cooperative project with Peter V. Tishler (Harvard Medical School), we plan to complete collection and pattern analysis (by two separate investigators) of 100 percent plus 21 controls and 0 percent (normal) controls. Coding and computer analysis will aim to improve the discrimination of quantitative dermal indices for diagnosis of Down's syndrome and Down's syndrome mosaicism. It is possible that correction of the dermal index score for familial influence ascertained through comparison of parent and sib prints with plus 21 index case, will increase discrimination of the score for presence of plus 21. Continued collection and analysis of prints from Down's syndrome parents will provide further data on the question of why older fathers have a greater tendency to show dermal microsymptoms. Further collection of prints from D/G and G/G translocation Down's syndrome may answer the question if quantitative dermal indices will distinguish degrees of trisomy in translocation Down's syndrome. Further collection of prints from patients with X long arm isochromosomes may answer the question if total digital ridge counts are changed. BIBLIOGRAPHIC REFERENCES: Priest, J.H.: Cytogenetics and Cell Culture. 2nd ed. Philadelphia, Lea & Febiger, publication date 1976; Priest, J.H., Blackston, R.D., and Au, K.-S., and Ray, S.L.: Differences in human X isochromosomes. J. Med. Genet., l975 (in press).